瑞芬太尼在老年和成年外科手术患者的药代动力学比较

目的研究瑞芬太尼在全麻老年患者和成年患者中的药代动力学特征,并进行比较。方法8名老年组和8名成年组外科手术患者静脉给予瑞芬太尼5μg.kg-1,不同时间取血并处理血样,用HPLC/MS/MS方法测定全血中瑞芬太尼浓度;用3P97程序进行药代动力学数据处理,并比较2组的异同。结果静脉注射瑞芬太尼的血药浓度-时间曲线符合二房室模型,老年组和成年组主要的药代动力学参数分别为:t1/2β=(22.32±4.13),(21.28±11.52)min;CL=(2.68±1.12),(2.19±0.35)L.min-1;AUC=(142.69±54.93),(189.83±37.34)ng.min.mL-1。结论老年组和成年组的药代动力学参数几乎没有显著性差异,老年患者临床麻醉给药时无需调整给药方案。     

液-质联用法测定瑞芬太尼在手术患者的全血浓度及其药代动力学

目的建立瑞芬太尼(麻醉药)在手术患者全血体内药物浓度的HPLC/MS/MS测定方法,并进行药代动力学研究。方法10名外科手术受试者静脉给予瑞芬太尼3~6μg·kg-1,用液质联用法测定全血中瑞芬太尼浓度,用3P87程序进行药代动力学数据处理。结果所建立瑞芬太尼全血药物浓度测定方法,回收率和精密度符合要求,符合二房室模型,其主要的药代动力学参数:Cmax=(32.57±7.38)ng·mL-1;t1/2β=(22.07±10.30)min;CL=(30.84±8.15)mL·(kg·min)-1;AUC=(192.80±35.72)ng·min·mL-1。结论测定方法简单、灵敏、准确,适于瑞芬太尼的药代动力学研究。     

舒芬太尼在心脏瓣膜置换术患者的药代动力学

目的 研究舒芬太尼(麻醉药)于体外循环下二尖瓣置换术(MVR)患者的药代动力学.方法 随机选择NYHA Ⅱ～Ⅲ级的MVR患者8例,麻醉后前臂静脉注射舒芬太尼5 μg·kg-1.在静脉注射舒芬太尼前和注射后1,3,5,10,20,30,60,120,180,240和360 min,采肝素抗凝血浆1 mL置入密封真空试管中,-80℃低温保存至分析.用液相色谱-质谱联用法测定血浆舒芬太尼浓度,3P97药理学程序计算药代动力学参数.结果 舒芬太尼在MVR患者的药代动力学符合三室开放模型,药物浓度与时间曲线可用三指数函数方程表示.主要药代动力学参数t1/2π=(1.39±0.36) min,t1/2 α=(14.03±4.46) min,t1/2 β=(410.34+41.33) min,Vc=(0.18±0.05) L·kg-1,Vd=(12.01±2.99) L·kg-1,CL=(0.02±4×10-3) L·kg-1·min-1和AUC=(253.85±55.76) ng·mL-1·min.结论 舒芬太尼在MVR患者药代动力学符合三室开放模型,体外循环与血液稀释及患者的心功能状态将影响其药代动力学特征.     

非房室模型统计矩方法测定妊娠晚期孕妇瑞芬太尼的药代动力学特点

目的计算妊娠晚期孕妇瑞芬太尼的药代动力学参数并分析其药代动力学特点。方法妊娠晚期行剖宫产手术孕妇10例,于硬膜外麻醉成功后静脉注射瑞芬太尼1μg／kg,于给药后1、2、3、5、7、10、20min分别采集孕妇动脉血2．0ml,采用液一液萃取毛细管气相色谱质谱法测定瑞芬太尼血药浓度,以非房室模型的统计矩方法测定妊娠晚期孕妇瑞芬太尼药代动力学参数分并析其药代动力学特点。结果此方法测定的妊娠晚期孕妇瑞芬太尼药代动力学特点为非房室模型,其药代动力学参数：t1/2（2．85±0．18）min,血浆药物浓度一时间曲线面积（AUC）：（0—20min）、（16．17±0．55）min·ng／ml,平均滞流时间（MRT）：（5．02±0．22）min,中央清除率（CL）：（59．99±2．17）ml·min^-1·kg^-1,建立在血浆药物浓度基础上的稳定表现分布表现容积（VSS）：（300．96±8．20）ml／kg。结论妊娠晚期孕妇其特殊的血液循环系统的改变,使瑞芬太尼在其体内清除率增高,消除半衰期延长。     

异丙酚全麻下瑞芬太尼在手术患者的药代动力学

目的研究瑞芬太尼(麻醉药)复合异丙酚靶控输注静脉全麻的临床药代动力学。方法选择24例靶控输注异丙酚全麻手术患者,以不同速度0.50,0.75,1.00μg·(kg·min)-1输注瑞芬太尼,取桡动脉血浆,用高效液相色谱-紫外法检测瑞芬太尼浓度,用DAS计算药代动力学参数。结果瑞芬太尼符合二室模型,3组患者的t1/2α、t1/2β、V1、V、CL比较无显著性差异(P>0.05),AUC(0-∞)、V、t1/2β和CL的RSD分别为33.42%,67.38%,51.22%和68.10%。结论瑞芬太尼不同输注速率对药代动力学无明显影响,但应注意个体化给药。     

海南地区国产瑞芬太尼静脉靶控输注的群体药代动力学研究

目的探讨国产瑞芬太尼在海南地区群体药代动力学变化规律及海南人国产瑞芬太尼最适靶控输注参数。方法前瞻性分析400例临床择期手术患者,通过建立液-液萃取毛细管气相色谱-质谱联用技术测定人血中瑞芬太尼浓度变化,计算瑞芬太尼靶控输注时群体药代动力学参数并分析其药代动力学特点。结果国产瑞芬太尼血药浓度-时间变化符合二房室模型,分布半衰期为(16.3±4.1)min,消除半衰期为(25.0±11.3)min,表观分布容积(70±12)L。结论国产瑞芬太尼海南地区群体药代动力学的变化规律与国外研究结果存在明显不同,有其特异性。     

老年与青壮年瑞芬太尼药代动力学差异比较

目的探讨老年与青壮年手术患者瑞芬太尼药代动力学参数差异。方法 ASAⅠ或Ⅱ级择期全麻老年及青壮年患者各8例,老年患者年龄62～81岁,青壮年患者年龄18～60岁,全麻诱导时静脉注射瑞芬太尼5μg/kg,于瑞芬太尼注射后1、2、3、5、7、10、15、20、25、30、45、60min分别采集动脉血1.0ml。采用液-液萃取毛细管气相色谱质谱法测定瑞芬太尼血药浓度。结果老年及青壮年患者主要药代动力学参数分别为：t1/2β：（20±9）min、（12±7）min,表现分布容积：（56±17）L、（44±10）L,血浆清除率：（2.7±0.4）L/min、（4.0±0.5）L/min。结论老年与青壮年患者瑞芬太尼药代动力学均符合二房室模型,消除半衰期、表观分布容积、清除率二者明显不同,提示老年与青壮年患者间瑞芬太尼群体药代动力学可能存在差异。     

择期外科手术期间国人瑞芬太尼的药物动力学研究

目的测定国人全身麻醉下瑞芬太尼的药物代谢动力学参数,并与既往国外文献进行比较。方法择期手术成年患者10例,在全麻诱导后静脉单次注射瑞芬太尼5-6μg·kg-1,随后在注射后0、1、2、3、5、7、10、15、20、25、30、45、60及90分钟抽取动脉血。采用液质联用测定法(HPLC/MS/MS)测定瑞芬太尼血药浓度。结果瑞芬太尼血药浓度-时间曲线变化符合二房室模型。平均分布半衰期(t1/2α)为1.56min(0.73~2.31),消除半衰期(t1/2β)为22.07min(9.71~36.07),清除率为(CL)2.149L·min-1(1.370~2.629),表观分布容积(Vd)为65.766L(23.069~108.379)。结论国人瑞芬太尼的药代动力学参数中表观分布容积明显大于国外研究结果,提示不同种族群体间的药代动力学变化存在差异。     

舒芬太尼在脱泵冠脉搭桥患者与先天性心脏病手术患者的药代动力学比较

目的 比较舒芬太尼(麻醉及术后镇痛药)在脱泵冠脉搭桥(OPCABG)与非紫绀先天性心脏病(NCHD)患者的药代动力学特征.方法 随机选择NYHA Ⅱ～Ⅲ级的心脏手术患者16例.按手术类型分为OPCABG(对照组)和NCHD组2组,每组8例.前臂一次性静脉注射舒芬太尼5 μg·kg-1.在静脉注射舒芬太尼前和注射后1,3,5,10,20,30,60,120,180,240和360 min,采肝素抗凝血浆1 mL置入密封真空试管中,-80℃低温保存直至分析.用液相色谱-质谱联用法测定血浆舒芬太尼浓度,3P97药理学程序计算药代动力学参数.结果 舒芬太尼在心脏手术患者血药浓度与时间曲线可用三指数函数方程表示,在分布项2组的t1/2π和t1/2α均无统计学意义(P＞0.05);t1/2β,Vd,CL和AUC 2组间差异有统计学意义(P＜0.01).结论 舒芬太尼在OPCABG和NCHD患者的药代动力学均可用三室开放模型描述,体外循环与血液稀释、心内分流性疾病和患者心功能状态将影响其药代动力学特征.     

异硫氰酸基雷公藤内酯醇活性代谢物雷公藤甲素在大鼠体内的药代动力学

目的观察大鼠单剂量静脉注射异硫氰酸基雷公藤内酯醇后雷公藤甲素的药代动力学。方法将大鼠分为2组(每组5只),分别单次尾静脉注射异硫氰酸基雷公藤内酯醇低、高剂量(4.25,8.50 mg·kg-1)。用LC-MS/MS法,检测大鼠血浆中雷公藤甲素的浓度,用BAPP 3.2软件计算药代动力学参数。结果低、高剂量的主要药代动力学参数如下:Cmax分别为(12.36±1.09),(55.74±21.20)ng·mL-1,Tmax均为(2.0±0.0)min,t1/2分别为(12.82±2.41),(13.73±2.84)h,AUC0-t分别为(245.93±42.50),(1034.45±471.76)ng·min.mL-1。结论在4.25～8.50 mg·kg-1,雷公藤甲素的药代动力学表现出非线性消除特征。     

Efficacy of gut lavage,hemodialysis, and hemoperfusion in the therapy of paraquat or diquat intoxication

Clinical and in vitro investigations were carried out to test the efficacy of gut lavage, hemodialysis, and hemoperfusion in the treatment of poisoning with paraquat or diquat. In a patient suffering from diquat intoxication 130 times more diquat was removed by gut lavage 30 h after ingestion than was removed by complete aspiration of the gastric contents.Determination of in vitro clearances for paraquat and diquat by hemodialysis showed that, at serum concentrations of 1–2 ppm, such as are frequently encountered in poisoning in man, toxicologically relevant quantities of herbicide cannot be removed from the body. At a concentration of 20 ppm, on the other hand, hemodialysis proved to be effective, the clearance being 70 ml/min at a blood flow rate of 100 ml/min. The efficacy of hemoperfusion with coated activated charcoal was on the whole better. Especially at concentrations around 1–2 ppm, the clearance values for hemoperfusion were some 5–7 times higher than those for hemodialysis.In a patient suffering from paraquat poisoning, both hemodialysis as well as hemoperfusion were carried out. The in vitro results could be confirmed: At serum concentrations of paraquat less than 1 ppm no clearance could be obtained by hemodialysis while by hemoperfusion with activated charcoal quite high clearance values were measured and the serum level dropped down to zero.

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Zusammenfassung Klinische Untersuchungen und Laboratoriumsversuche wurden durchgeführt, um die Wirksamkeit von Darmspülung, Hämodialyse und Hämoperfusion bei Paraquat- und Deiquat-Vergiftungen zu prüfen.Bei einem Patienten wurde 30 Std nach Deiquat-Aufnahme durch Darmspülung 130mal mehr Deiquat entfernt als durch vollständige Aspiration des Mageninhaltes. In vitro-Versuche ergaben, daß bei Blutserumkonzentrationen von 1–2 ppm, die bei Vergiftungen oft gemessen werden, durch Hämodialyse keine toxikologisch relevanten Paraquat- oder Deiquat-Mengen entfernt werden können. Dagegen erwies sich die Hämodialyse bei 20 ppm und einer Blutumlaufgeschwindigkeit von 100 ml/min mit einer Clearance von 70 ml/min als wirksam. Die Hämoperfusion mit beschicheter Aktivkohle war in diesen Versuchen aber eindeutig überlegen, denn insbesondere bei Konzentrationen um 1–2 ppm waren die Clearance-Werte 5–7mal höher als bei der Hämodialyse.Die in vitro-Ergebnisse wurden bei einem Patienten mit einer Paraquat-Vergiftung bestätigt: Bei Konzentrationen unter 1 ppm war die Hämodialyse wirkungslos, während durch Hämoperfusion relativ hohe Clearance-Werte erreicht wurden, so daß der Serumspiegel rasch unter die Nachweisgrenze abfiel.

     

In vitro studies on sterically stabilized liposomes (SL) as enzyme carriers in organophosphorus (OP) antagonism

This study describes a new approach for organophosphorous (OP) antidotal treatment by encapsulating an OP hydrolyzing enzyme, OPA anhydrolase (OPAA), within sterically stabilized liposomes. The recombinant OPAA enzyme was derived from Alteromonas strain JD6. It has broad substrate specificity to a wide range of OP compounds: DFP and the nerve agents, soman and sarin. Liposomes encapsulating OPAA (SL)* were made by mechanical dispersion method. Hydrolysis of DFP by (SL)* was measured by following an increase of fluoride ion concentration using a fluoride ion selective electrode. OPAA entrapped in the carrier liposomes rapidly hydrolyze DFP, with the rate of DFP hydrolysis directly proportional to the amount of (SL)* added to the solution. Liposomal carriers containing no enzyme did not hydrolyze DFP. The reaction was linear and the rate of hydrolysis was first order in the substrate. This enzyme carrier system serves as a biodegradable protective environment for the recombinant OP-metabolizing enzyme, OPAA, resulting in prolongation of enzymatic concentration in the body. These studies suggest that the protection of OP intoxication can be strikingly enhanced by adding OPAA encapsulated within (SL)* to pralidoxime and atropine.     

Synthesis,Cytotoxicity and Antileishmanial Activity of Some N-(2-(indol-3-yl)ethyl)-7-chloroquinolin-4-amines

We report herein the condensation of 4,7-dichloroquinoline (1) with tryptamine (2) and D-tryptophan methyl ester (3) . Hydrolysis of the methyl ester adduct (5) yielded the free acid (6) . The compounds were evaluated in vitro for activity against four different species of Leishmania promastigote forms and for cytotoxic activity against Kb and Vero cells. Compound (5) showed good activity against the Leishmania species tested, while all three compounds displayed moderate activity in both Kb and Vero cells.     

Steroidal sapogenin contents in some domestic plants

In order to find out the values of the steroid resources for the future use. the compositions and contents of steroidal sapogenins from 13 domestic plants have been investigated. As a result,Dioscorea nipponica, D. quinqueloba andSmilax china were found to have large amount of diosgenin. And pennogenin inTrillium kamtschaticum andParis verticillata, yuccagenin inAllium fistulosum, hecogenin inAgave americana and neochlorogenin inSolanum nigum were appeared to be major steroidal sapogenins.     

Aquatic Insects and Trace Metals: Bioavailability,Bioaccumulation, and Toxicity

Abstract

The uptake of metals from food and water sources by insects is thought to be additive. For a given metal, the proportions taken up from water and food will depend both on the bioavailable concentration of the metal associated with each source and the mechanism and rate by which the metal enters the insect. Attempts to correlate insect trace metal concentrations with the trophic level of insects should be made with a knowledge of the feeding relationships of the individual taxa concerned. Pathways for the uptake of essential metals, such as copper and zinc, exist at the cellular level, and other nonessential metals, such as cadmium, also appear to enter via these routes. Within cells, trace metals can be bound to proteins or stored in granules. The internal distribution of metals among body tissues is very heterogeneous, and distribution patterns tend to be both metal and taxon specific. Trace metals associated with insects can be both bound on the surface of their chitinous exoskeleton and incorporated into body tissues. The quantities of trace meals accumulated by an individual reflect the net balance between the rate of metal influx from both dissolved and particulate sources and the rate of metal efflux from the organism. The toxicity of metals has been demonstrated at all levels of biological organization: cell, tissue, individual, population, and community. Much of the literature pertaining to the toxic effects of metals on aquatic insects is based on laboratory observations and, as such, it is difficult to extrapolate the data to insects in nature. The few experimental studies in nature suggest that trace metal contaminants can affect both the distribution and the abundance of aquatic insects. Insects have a largely unexploited potential as biomonitors of metal contamination in nature. A better understanding of the physico-chemical and biological mechanisms mediating trace metal bioavailability and exchange will facilitate the development of general predictive models relating trace metal concentrations in insects to those in their environment. Such models will facilitate the use of insects as contaminant biomonitors.